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Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood.
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MedLine Citation:
PMID:  12676612     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fetal and childhood exposures to widely used organophosphate pesticides, especially chlorpyrifos (CPF), have raised concerns about developmental neurotoxicity. Previously, biomarkers for brain cell number, cell packing density, and cell size indicated that neonatal rats were more sensitive to CPF than were fetal rats, yet animals exposed prenatally still developed behavioral deficits in adolescence and adulthood. In the present study, we administered CPF to pregnant rats on gestational days 17-20, using regimens devoid of overt fetal toxicity. We then examined subsequent development of acetylcholine systems in forebrain regions involved in cognitive function and compared the effects with those on general biomarkers of cell development. Choline acetyltransferase, a constitutive marker for cholinergic nerve terminals, showed only minor CPF-induced changes during the period of rapid synaptogenesis. In contrast, hemicholinium-3 binding to the presynaptic choline transporter, which is responsive to nerve impulse activity, displayed marked suppression in the animals exposed to CPF; despite a return to nearly normal values by weaning, deficits were again apparent in adolescence and adulthood. There was no compensatory up-regulation of cholinergic receptors, as m2-muscarinic cholinergic receptor binding was unchanged. CPF also elicited delayed-onset alterations in biomarkers for general aspects of cell integrity, with reductions in cell packing density, increases in relative cell size, and contraction of neuritic extensions; however, neither the magnitude nor timing of these changes was predictive of the cholinergic defects. The present findings indicate a wide window of vulnerability of cholinergic systems to CPF, extending from prenatal through postnatal periods, occurring independently of adverse effects on general cellular neurotoxicity.
Authors:
Dan Qiao; Frederic J Seidler; Charlotte A Tate; Mandy M Cousins; Theodore A Slotkin
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Environmental health perspectives     Volume:  111     ISSN:  0091-6765     ISO Abbreviation:  Environ. Health Perspect.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-04     Completed Date:  2003-07-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0330411     Medline TA:  Environ Health Perspect     Country:  United States    
Other Details:
Languages:  eng     Pagination:  536-44     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / analysis
Brain / drug effects*,  growth & development*,  physiology
Chlorpyrifos / administration & dosage,  adverse effects*
Choline O-Acetyltransferase / analysis*,  pharmacology*
Cholinesterases / analysis,  pharmacology
Cognition Disorders / etiology*
Female
Insecticides / administration & dosage,  adverse effects*
Pregnancy
Prenatal Exposure Delayed Effects*
Rats
Rats, Sprague-Dawley
Receptors, Cholinergic / biosynthesis
Up-Regulation
Grant Support
ID/Acronym/Agency:
ES10356/ES/NIEHS NIH HHS; ES10387/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Insecticides; 0/Receptors, Cholinergic; 2921-88-2/Chlorpyrifos; EC 2.3.1.6/Choline O-Acetyltransferase; EC 3.1.1.8/Cholinesterases
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Journal Information
Journal ID (nlm-ta): Environ Health Perspect
ISSN: 0091-6765
Article Information
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Print publication date: Month: 4 Year: 2003
Volume: 111 Issue: 4
First Page: 536 Last Page: 544
ID: 1241441
PubMed Id: 12676612

Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood.
Dan Qiao
Frederic J Seidler
Charlotte A Tate
Mandy M Cousins
Theodore A Slotkin
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.


Article Categories:
  • Research Article


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